Obstructive sleep apnea (OSA) presents perioperative challenges with increased risk for complications. Floppy eyelid syndrome (FES) is associated with OSA yet has not been addressed perioperatively. The current standard for perioperative OSA screening includes assessing patient risk factors or the STOP-BANG tool, which requires an active participant. We aimed to confirm a connection between FES and OSA in presurgical patients and develop a screening method appropriate for patients with perioperative OSA risk. 162 presurgical pre-anesthesia clinic patients were enrolled. Screening questions determined eligibility. Those who were pregnant or aged < 19 were excluded. Control group included those with a STOP-BANG score < 3. Experimental group included those with BMI > 35 and OSA diagnosis. Examiners photographed participants’ eyes with vertical and horizontal retraction while two blinded ophthalmologists used a grading scale to review grade of eyelid laxity. Differences in habitus, ASA score, and hypertension as a comorbidity were significant. Sensitivity of FES screening was 52% (CI 37–66%) and specificity was 56% (CI 46–66%) for reviewer 1. For reviewer 2, sensitivity was 48% (CI 28–69%) and specificity was 72% (CI 60–81%). Negative predictive value was 86% (CI 81–90) for reviewer 1 and 88% (CI 83–92%) for reviewer 2. Inter-rater agreement was moderate. While specificity and sensitivity were lower than anticipated, negative predictive value was high. Given this strong negative predictive value, our findings indicate using eyelid retraction to screen for FES has perioperative clinical utility. These findings encourage further research addressing the connection of lid laxity/FES to OSA. • Aimed to investigate if a FES screening tool could identify perioperative OSA risk. • Negative predictive value for FES with OSA was 86%. • Observing periocular lid laxity has clinical utility; is feasible in any patient.

Purpose: The identification of target pathways to block excessive angiogenesis while simultaneously restoring physiological vasculature is an unmet goal in the therapeutic management of ischemic retinopathies. pNaKtide, a cell-permeable peptide that we have designed by mapping the site of α1 Na/K-ATPase (NKA)/Src binding, blocks the formation of α1 NKA/Src/reactive oxygen species (ROS) amplification loops and restores physiological ROS signaling in a number of oxidative disease models. The aim of this study was to evaluate the importance of the NKA/Src/ROS amplification loop and the effect of pNaKtide in experimental ischemic retinopathy. Methods: Human retinal microvascular endothelial cells (HRMECs) and retinal pigment epithelium (ARPE-19) cells were used to evaluate the effect of pNaKtide on viability, proliferation, and angiogenesis. Retinal toxicity and distribution were assessed in those cells and in the mouse. Subsequently, the role and molecular mechanism of NKA/Src in ROS stress signaling were evaluated biochemically in the retinas of mice exposed to the well-established protocol of oxygen-induced retinopathy (OIR). Finally, pNaKtide efficacy was assessed in this model. Results: The results suggest a key role of α1 NKA in the regulation of ROS stress and the Nrf2 pathway in mouse OIR retinas. Inhibition of α1 NKA/Src by pNaKtide reduced pathologic ROS signaling and restored normal expression of hypoxia-inducible factor 1-α/vascular endothelial growth factor (VEGF). Unlike anti-VEGF agents, pNaKtide did promote retinal revascularization while inhibiting neovascularization and inflammation. Conclusions: Targeting α1 NKA represents a novel strategy to develop therapeutics that not only inhibit neovascularization but also promote physiological revascularization in ischemic eye diseases.